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Long-term hyperglycaemia decreases gastrocnemius susceptibility to permeability transition
José Lumini-Oliveira1, António Ascensão, Cláudia V Pereira
1Research Centre in Physical Activity, Health and Leisure, Faculty of Sport Sciences, University of Porto, Porto, Portugal.
Long-term hyperglycemia in rats reduced gastrocnemius mitochondrial respiratory control and calcium-dependent mitochondrial permeability transition pore (MPTP) opening. This suggests organ-specific mitochondrial effects of high blood sugar.
Area of Science:
- Mitochondrial physiology
- Diabetic complications
- Skeletal muscle biology
Background:
- Hyperglycemia is linked to skeletal muscle dysfunction via mitochondrial complications.
- Investigating long-term hyperglycemia's impact on gastrocnemius mitochondria is crucial.
Purpose of the Study:
- To analyze the effect of long-term severe hyperglycemia on gastrocnemius mitochondrial bioenergetics.
- To determine the susceptibility to mitochondrial permeability transition pore (MPTP) opening under hyperglycemic conditions.
Main Methods:
- Adult male Wistar rats were divided into control and diabetic groups (n=8).
- Diabetes was induced via streptozotocin (STZ) injection.
- Mitochondrial function, MPTP induction, and caspase 9 activity were assessed after 18 weeks.
Main Results:
- STZ treatment decreased respiratory control ratio with complex I substrates.
- Maximal mitochondrial membrane potential (Delta psi) showed no significant difference, but increased during ADP-induced depolarization with succinate.
- Mitochondria from STZ-treated rats exhibited decreased susceptibility to calcium-induced MPTP opening and reduced caspase 9-like activity.
Conclusions:
- Eighteen weeks of STZ-induced hyperglycemia reduced gastrocnemius mitochondrial respiratory control and calcium-dependent MPTP opening.
- Mitochondrial effects of hyperglycemia appear to be time- and organ-specific.
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